Investigators Use Stem Cells to Study Rare Pediatric Brain Tumors

By Julie Grisham,

Monday, December 1, 2014

Pictured: Viviane Tabar

Investigators have created the first-ever genetically engineered model of cancer made from human embryonic stem cells in culture.

Since the late 1990s, when researchers first reported a technique to isolate and grow human embryonic stem cells, known as ES cells, in culture, experts have deliberated the many possible uses for them. Among these are developing better systems for studying disease processes and creating new cells and tissues to replace those lost to disease or injury.

In a paper published recently in Science, a team from Memorial Sloan Kettering and elsewhere has reported the first-ever genetically engineered model of cancer created from human ES cells. Research enabled by the advance has given hope of a treatment for a rare pediatric brain tumor called diffuse intrinsic pontine glioma (DIPG).

“Recent sequencing studies have provided clues about some of the genetic mutations that characterize these aggressive, incurable tumors, but how the mutations lead to cancer has not been understood,” says physician-scientist Viviane Tabar, the senior author of the study. “We decided to model DIPG using ES cells in an effort to decipher the mechanisms of tumor formation.”

Transforming Stem Cells

The excitement surrounding human ES cells arises partly from the fact that these cells are pluripotent: They have the ability to develop into almost any cell type in the body. Dr. Tabar is a neurosurgeon, and an area of focus in her laboratory for the past several years has been studying the processes by which ES cells can be induced to form different types of brain cells.

On the molecular level, the cells we created resembled brain tumors from patients.
Viviane Tabar Physician-Scientist

The first step in the current study was transforming ES cells into the type of brain stem cells that are present in young children. The investigators then introduced into those brain stem cells the cancer-causing genes (also called oncogenes) that are expressed in DIPG.  When injected into the brain stems of mice, the cells formed tumors that exhibited many of the features of human DIPG.

“On the molecular level, the cells we created resembled brain tumors from patients,” Dr. Tabar explains. “Once they began growing in the mice, we could use them to test drugs that could potentially kill cancer cells in patients.”

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A Focus on Epigenetics

The investigators screened for drugs that could kill DIPG cells while sparing healthy brain stem cells and zeroed in on a single compound, called menin inhibitor-2 (MI-2). Menin is a tumor suppressor — a type of protein that normally prevents cancer growth — and has been linked to several other types of cancer. Specifically, it plays a role in histone modification, a type of epigenetic change that, by adjusting the activity of certain genes, can influence cells’ ability to proliferate and grow out of control.

The investigators tested MI-2 in the mice with DIPG and discovered that it led to significant shrinkage of the brain tumors. They then confirmed that the drug could potentially be effective against the human disease by killing tumor cells that had been removed from patients and grown in a dish in the lab.

“The work shows that an ES-based system for cancer modeling may have significant advantages over tumor cell cultures and earlier types of mouse models,” Dr. Tabar concludes. “In addition, it offers hope for a potential therapy against DIPG, a disease that has proven intractable against hundreds of other drugs and that carries a very short life expectancy.”

David Allis, a Tri-Institutional Professor in MSK’s Molecular Biology Program, a professor at The Rockefeller University, and a leading expert on the study of histones and epigenetic changes, was co-author on the new study. Kosuke Funato, a postdoctoral scientist in Dr. Tabar’s lab, was the first author.

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This research was funded by the Brain Tumor Center and the Center for Stem Cell Biology at MSK; The Rockefeller University; the Geoffrey Beene Cancer Center; the Starr Cancer Consortium; and the New York State Stem Cell Board.


I would like to join the battle against dipg
I lost my daughter from it
If any help require do mail me
From india.

My son was diagnosed in May 2014 with dipg..will there be any trails coming up with the use of MI2. We would be interested. We arent willing to give up yet

Cindy, we are sorry to hear about your son's diagnosis. We asked Dr. Tabar, and she said her team is working hard on pre-clinical studies with a goal of moving the compound into clinical trials as soon as possible, but unfortunately there are currently no trials with this compound. Thank you for your comment.

Hello my question is the same as above, My 7 year old son Jared, was diagnosed last week with DIPG. We have banked his stem cell at birth. We live in Montreal, Canada, can you let me know as soon as any clinical trials start on MI2. There has to be a cure for this terrible disease.

Simon, we are very sorry about your son's diagnosis. The best way to keep track of all clinical trials for DIPG is to check, which is run by the National Institutes of Health (it includes trials run in the U.S. and other countries as well, including by Memorial Sloan Kettering). Here is the page for DIPG trials:

Is there a way to receive this off study?

Mycke, thank you for reaching out. Unfortunately, this potential treatment is still in preclinical (animal) studies, and not even in clinical trials at all. It is still in the investigative stage.

Do they have a timeline as to when they will be trying to have the drug humanized?

Mycke, unfortunately it's too early in the process to say how long it will take before the drug will be ready for testing in humans.

Thumbs up MSK and for all the team working on this issue. You are giving hope for too many people struggling against brain cancer. Thank you.

Please offer to our kids a hope and a chance to live their life away from this monster daughter Fotini didn't have it. She lost her life after struggling for 14 months and she stayed for ever 11 years old.
I am at your disposal for any help and contribution needed- despite the geographical distance (Athens, Greece) - unfortunately dipg is worldwide..

Dear Landa, we are very sorry for your loss and appreciate your offer to support MSK. If you are interested in making a contribution and would like more information, please visit our Giving pages at or email our Development office at Thank you for your comment.

Please, we beg you to have this treatment ready as soon as you can.
it's our only daughter Mary-Lynn was diagnosed with DIPG. She is a real angel she makes every body happy around her. she still tell jokes to Drs. and Nurses. She is only 9.4 y/o. We were referred to you by Sick Kids Hospital for CED OF124I-8H9 and you said it will cost us average $100000.00 USA Dollars. We did fund raising for our daughter and got less that 3000.00 so far. Does this mean that if people don't have enough money they can't even have an experimental medication?
thanks for your feed back. Good luck for your efforts to treat DIPG for all diagnosed kids.

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